Clinical sequelae following COVID19 can persist months after initial infection and significantly affect patients' quality of life. The pathomechanisms and predictors for their course remain unclear. Here, we explored markers of systemic inflammation and pulmonary damage, and their association with clinical characteristics in patients with long COVID.

Outpatients presenting with persisting symptoms after SARS-CoV2 infection were prospectively recruited. Serum markers of inflammation and pulmonary damage, and their association with symptom burden, clinical and lung function parameters were assessed for up to one year after infection.

We included data from 235 patients (median age 48 [IQR 38-56] y, 65% female) during 503 visits. Acute COVID19 had mostly been mild to moderate, yet symptom burden at inclusion was high, with fatigue (81.7%) and shortness of breath (75.3%) being most common. FEV1% was below 80% in 11.6% of visits. Maximum inspiratory muscle strength (MIP) was impaired during 54.5% of visits, and negatively correlated with fatigue (ρ=-0.16, p=0.001) and cumulative symptom scores (ρ=-0.14, p=0.024). Levels of IL8, IL1β, IL10, TGFβ, surfactant protein D, and club cell protein 16 (CC16) showed little to no change over time and did not differ depending on severity of acute COVID19. CC16 levels were lower in patients with fatigue (7.1 [IQR 5.2-8.9] vs. 7.7 [IQR 6.4-10.8] ng/ml, p=0.008), and negatively correlated with symptom scores (ρ=-0.16, p=0.025).

Our results confirm the high burden and heterogeneity of symptoms in patients with long COVID. Lack of anti-inflammatory proteins such as CC16 associated with symptoms may represent a pathogenetic factor.